11-102715329-GTC-ATA

Variant names:

• chr11-102715329-GTC-ATA
• NM_002424.3:c.1009_1011delGACinsTAT
• MMP8 p.Asp337Tyr

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002424.3(MMP8):​c.1009_1011delGACinsTAT​(p.Asp337Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D337H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MMP8 NM_002424.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70
• Publications: 0 publications found

Genes affected

MMP8 (HGNC:7175): (matrix metallopeptidase 8) This gene encodes a member of the matrix metalloproteinase (MMP) family of proteins. These proteins are involved in the breakdown of extracellular matrix in embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Proteolysis at different sites on this protein results in multiple active forms of the enzyme with distinct N-termini. This protein functions in the degradation of type I, II and III collagens. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002424.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP8	NM_002424.3	MANE Select	c.1009_1011delGACinsTAT	p.Asp337Tyr	missense	N/A	NP_002415.1	P22894
	MMP8	NM_001304441.2		c.940_942delGACinsTAT	p.Asp314Tyr	missense	N/A	NP_001291370.1
	MMP8	NM_001304442.2		c.940_942delGACinsTAT	p.Asp314Tyr	missense	N/A	NP_001291371.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP8	ENST00000236826.8	TSL:1 MANE Select	c.1009_1011delGACinsTAT	p.Asp337Tyr	missense	N/A	ENSP00000236826.3	P22894
	MMP8	ENST00000438475.2	TSL:5	c.934_936delGACinsTAT	p.Asp312Tyr	missense	N/A	ENSP00000401004.2	H7C1M3
	MMP8	ENST00000528662.6	TSL:5	n.*986_*988delGACinsTAT		non_coding_transcript_exon	Exon 9 of 12	ENSP00000431431.2	E9PL87

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-102586060;